Alveolar Rhabdomyosarcoma IS characterised by a t(2;13)(q35;qI4) chromosome
trartslocation, which leads to the fusion of the P AX3 artd the FKHR genes. The resulting
fusion gene encodes a chimeric protein which has aberrant transcriptional activity. The
data here describes the molecular definition of the genomic breakpoints on both
derivative chromosomes in one case and the derivative chromosome 13 breakpoints in
two other cases. The DNA sequences adjacent to the breakpoints on the derivative
chromosome 13 are remarkable for their resemblartce to recognition sequences for the
protein trartslin. Electrophoretic mobility shift studies (EMSA) confirm that these
sequences bind translin. These findings suggest that translin may not only be important
in the genesis of chromosomal trartslocations in lymphoid malignancy, but also in
trartslocations found in solid tumours.
Mutation analysis of tumour samples and cell lines from patients with embryonal and
alveolar rhabdomyosarcoma suggests that there are no subtle disease associated
mutations within the PAX3 gene that could contribute towards the neoplastic state.